The renal medulla exerts an endocrine-type antihypertensive function. The cells performing this function appear to be the renomedullary interstitial cells (RIC). This antihypertensive action has been demonstrated in a variety of hypertensive states, including Na-volume loaded types and accelerated-malignant type. The action, therefore is quite powerful. The mediator of this function is unknown. However, two antihypertensive lipids can be derived from fresh renal medulla. One is polar (APRL) and the other neutral (ANRL). APRL exerts both an acute and a prolonged depressor effect in hypertensive animals. ANRL exerts mainly the prolonged effect. APRL has been purified to the extent that its structure should be forthcoming. ANRL requires further purification for such purpose. A monolayer tissue culture of JG-like cells has been derived. These cells have peripheral dense bodies, myofibrils and secretory granules (as well as lysozomes). The cells secrete renin into the culture media. The transplantation of the cell line into normal syngeneic recipients causes hypertension that reaches its maximum in 10-14 days. During the evolution of this hypertension the plasma renin concentration remains normal (normoreninemic hypertension). We are attempting to evaluate the possibility of a "push-pull" effect between the prohyertensive JG-like cells and the antihypertensive RIC.